The effects of lowering blood oxygen affinity on hemodynamics (blood pressure, cardiac output and organ blood flow), myocardial function (left ventricular dp/dt at selected times during systole), myocardial metabolism (oxygen consumption, lactate and pyruvate changes in cornary blood), and myocardial oxygen supply (blood flow, coronary arterial oxygen concentration, coronary venous oxygen concentration and PO2, and oxygen consumption) will be studied in trained dogs and inlightly anesthetized rhesus monkeys. Measurements will be made before and after decreasing blood oxygen affinity in animals at rest and, in another group, during exercise (simulated by electrical stimulation of the extremities in monkeys). Our purpose is to investigate the hypothesis that decreasing blood oxygen affinity will improve tissue oxygen supply and/or reserve and that this will be especially true in the myocardium because of a fall in cardiac output. Methods for lowering blood oxygen affinity will first be developed in vitro, then studied in dogs and monkeys for toxic and physiological effects. If evidence of an improved myocardial oxygen supply results from the animal studies, and no evidence of toxicity, or of unwanted physiological effects is detected, a method developed for human blood in vitro will be applied to patients with angina pectoris, evaluating the effect of decreasing the blood oxygen affinity on exercise tolerance and red cell metabolism in vivo.